The primary objective of the NIEHS Superfund Basic Research Program (SBRP) is to understand the human health and environmental risks associated with hazardous waste sites, with the goal of more accurately assessing risks and more efficiently remediating hazardous waste sites. Since its inception, the UNC SBRP has focused its multidisciplinary research on addressing scientific issues that underpin the assessment of human risk and the development of improved methods for remediation of hazardous waste sites, in the proposed research, we will further advance this goal through the following objectives: 1) apply new molecular and analytical tools in a systems biology framework to understand critical pathways for environmental disease and bioremediation;2) develop biomarkers of exposure and effect for humans and experimental models of environmental disease;3) use this knowledge to elucidate the modes of action for major chlorinated hydrocarbons and polycyclic aromatic hydrocarbons;4) examine the effects of dose-response on such modes of action;5) evaluate and understand genetic susceptibility to hazardous chemicals;6) determine the factors controlling dermal absorption of polycyclic aromatic hydrocarbons and the relationship of internal dose to both skin and systemic exposure;and 7) develop and evaluate remediation methods in complex, field-relevant systems for their potential to reduce overall human exposures and risks. These objectives will be accomplished through six diverse, but highly interdigitated research projects, two research support cores, a research translation core, a training core and an administrative core.